Septins as diagnostic markers for a subset of human asthenozoospermia.
OBJECTIVE
Septins are the major constituents of the annulus, a submembranous ring that separates the middle and principal pieces of spermatozoa. We previously reported its essential role in spermiogenesis and reproduction in mice. In the current study we investigated septin abnormality in infertile men.


METHODS
Semen samples from 108 infertile patients and 21 healthy volunteers were analyzed for sperm concentration and motility. Spermatozoa were immunostained for the 2 representative septin subunits SEPT4 and SEPT7. Peripheral blood DNA from 8 patients with asthenozoospermia who had defective SEPT4 and/or SEPT7 labeling in the annuli was analyzed by direct sequencing. Clinical information and a followup review of pregnancy were obtained retrospectively from medical records.


RESULTS
Specific antibodies for SEPT4 and SEPT7 consistently labeled the annuli in spermatozoa from the 21 healthy volunteers, while 14 of 108 samples (13%) from infertile patients showed defective labeling. In 33 patients with asthenozoospermia 10 samples (30%) demonstrated defective labeling for SEPT4 and/or SEPT7. We could not detect exon mutations in the SEPT4 gene by sequencing peripheral blood DNA from 8 patients with asthenozoospermia who had defective SEPT4 and/or SEPT7 labeling. During followup 8 of 14 patients (57%) with SEPT4 and/or SEPT7 labeling defects achieved successful pregnancies.


CONCLUSIONS
Annulus defects were found exclusively in infertile patients. Although their prognoses do not differ from those without annulus defects, annulus labeling by septin antibodies may serve as an index for classifying a subset of spermatogenesis defects and monitoring sperm quality.
Sugino
Yoshio
Y
Department of Urology, Kyoto University Graduate School of Medicine, Kyoto, Japan.
Ichioka
Kentaro
K
Soda
Takeshi
T
Ihara
Masafumi
M
Kinoshita
Makoto
M
Ogawa
Osamu
O
Nishiyama
Hiroyuki
H
D053627:Asthenozoospermia / Q000175:diagnosis*; D015415:Biomarkers / Q000032:analysis; D018797:Cell Cycle Proteins / Q000032:analysis*; D003598:Cytoskeletal Proteins / Q000032:analysis*; D020558:GTP Phosphohydrolases / Q000032:analysis*; D006801:Humans; D008297:Male; D012189:Retrospective Studies; D058112:Septins; D013081:Sperm Motility; D013094:Spermatozoa / Q000737:chemistry*
D015415:Biomarkers; D018797:Cell Cycle Proteins; D003598:Cytoskeletal Proteins; D020558:GTP Phosphohydrolases; C492027:SEPTIN4 protein, human; C113158:SEPTIN7 protein, human; D058112:Septins